Dendrimer-based excipients for the attenuation of protein aggregation
One aspect of the invention is a salt comprising guanidinium groups, as shown in formula I. Another aspect of the invention is a salt comprising guanidinium groups, as shown in formula II. Another aspect of the invention is a salt comprising guanidinium groups, as shown in formula III. Another aspect of the invention is a salt comprising guanidinium groups, as shown in formula IV. Yet another aspect of the invention is a salt comprising guanidinium groups, as shown in formula I, II, III, and IV further comprising independently for each occurrence citrate, phosphate, or sulfate anion. Also disclosed are compositions comprising a protein and a salt comprising guanidinium groups, as shown in formula I, II, III, and IV. Also provided are methods of increasing shelf life of an aqueous solution of a protein and decreasing the amount of protein aggregation in an aqueous solution of a protein.
1. A salt, comprising a plurality of anions; and a cation represented by formula I:
wherein, independently for each occurrence,
each anion is
Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
Y is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
X 1 is
X 2 is
and
X 3 is
2. A salt, comprising a plurality of anions; and a cation represented by formula II:
wherein, independently for each occurrence,
each anion is
Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
Y is —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
X 1 is
X 2 is
and
X 3 is
3. A salt, comprising a plurality of anions; and a cation represented by formula III:
wherein, independently for each occurrence,
each anion is
X 1 is
X 2 is
X 3 is
and
X 4 is
4. A salt, comprising a plurality of anions; and a cation represented by formula IV:
wherein, independently for each occurrence,
each anion is
Z is —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, or —CH 2 CH 2 CH 2 CH 2 CH 2 —;
X 1 is
X 2 is
X 3 is
and
X 4 is
5. The salt of claim 1 , wherein X 1 is
6. The salt of claim 1 , wherein X 1 is
and X 2 is
7. The salt of claim 1 , wherein X 1 is
and X 2 is
8. The salt of claim 1 , wherein Z is —CH 2 CH 2 —.
9. The salt of claim 1 , wherein Y is —CH 2 CH 2 —.
10. The salt of claim 1 , wherein Y is —CH 2 CH 2 —; and Z is —CH 2 CH 2 —.
11. The salt of claim 1 , wherein each anion is
12. The salt of claim 1 , wherein each anion is
13. The salt of claim 1 , wherein each anion is
14. A composition, comprising a protein; and a salt of claim 1 .
15. The composition of claim 14 , wherein the protein is selected from the group consisting of antibodies and enzymes.
16. A method of increasing shelf life of an aqueous solution of a protein, comprising:
combining an aqueous solution of a protein and an effective amount of a salt of claim 1 .
17. The method of claim 16 , wherein the protein is selected from the group consisting of antibodies and enzymes.
18. A method of decreasing the amount of protein aggregation in an aqueous solution of a protein, comprising:
combining an aqueous solution of a protein and an effective amount of a salt of claim 1 .
19. The method of claim 18 , wherein the protein is selected from the group consisting of antibodies and enzymes.